FIELD OF THE INVENTION
This invention is directed to new organic intermediate compounds and is particularly concerned with [3-(halomethyl)-4H-1,2,4-triazol-4-yl]benzophenones.
The novel compounds and the process of production therefor can be illustratively represented as follows: ##STR2## wherein R is hydrogen or alkyl of 1 to 3 carbon atoms, inclusive; wherein R.sub.2 is hydrogen, fluoro, or chloro; wherein R.sub.3 is hydrogen or fluoro with the proviso that R.sub.3 is not fluoro, if R.sub.2 is chloro; wherein R.sub.4 is hydrogen, fluoro, chloro, bromo, trifluoromethyl or nitro; and wherein X is chloro, bromo, iodo.
The more desirable products of this invention are of the formula VIA: ##STR3## wherein R' is hydrogen or methyl; wherein R.sub.2 is hydrogen, chloro, or fluoro; wherein R.sub.3 is hydrogen or fluoro with the proviso that R.sub.3 is not fluoro if R.sub.2 is chloro; wherein R.sub.4' is hydrogen, fluoro, chloro, trifluoromethyl, and nitro; and wherein X is chloro, bromo, or iodo.
The most desirable products are of the formula VIB: ##STR4## wherein R.sub.2' is hydrogen or chloro; and wherein R.sub.4' is chloro or fluoro; and wherein X' is chloro or bromo.
The products of formula VI are useful per se as tranquilizers but their principal use is as intermediates for compounds of formula VII which are extremely potent tranquilizers. The compounds of formula VII are obtained from those of formula VI by the following reaction: ##STR5## wherein R, R.sub.2, R.sub.3, R.sub.4, and X have the same significance as above.
The process of this invention comprises:
1. Refluxing a 2-chloro-4-phenylquinoline (I) with hydrazine hydrate to give a 2-hydrazino-4-phenylquinoline (II);
2. Refluxing the 2-hydrazino-4-phenylquinoline (II) with a trialkyl orthoacylate e.g. with triethyl orthoformate, triethyl orthoacetate, triethyl orthopropionate or trimethyl orthobutyrate, in an inert organic solvent to give the corresponding 1-substituted-5-phenyl-s-triazolo-[4,3-a]quinoline (III);
3. Treating (III) with an oxidizing agent or system such as ruthenium dioxide and sodium periodate or ozone in an inert solvent at low temperature to give a mixture containing mainly a 2-(3-substituted-4H-1,2,4-triazol-4-yl)benzophenone(IV);
4. Treating (IV) with formaldehyde to obtain a 2-[3-(hydroxymethyl-5-substituted-4H-1,2,4-triazol-4-yl]benzophenone;
5. Converting alcohol V to a halide with a halogenating agent such as phosphorus tribromide, phosphorus oxychloride, phosphorus triiodide, or thionyl chloride to obtain the corresponding 2-[3-(halomethyl)-5-substituted-4H-1,2,4-triazol-4-yl]benzophenone (VI);
6. And treating (VI) with ammonia to give the corresponding end product, 1-substituted-6-phenyl-4H-s-triazolo[4,3-a]-[1,4]benzodiazepine VII.